The proposed research seeks to discover, establish, and study new reactions and enzymes in the metabolism of hydroxyamino acids as well as of their metabolites and/or related compounds; to synthesize and test potential inhibitors for control of metabolic or enzymic processes; to examine the relationship of enzyme structure and function; and to study enzyme regulation. Examples are the study of: the metabolism of gamma-hydroxyglutamic acid and alpha-keto-gamma-hydroxyglutaric acid which compounds are intermediates in the mammalian metabolism of hydroxyproline, a major amino acid component of collagen; the metabolism of beta, gamma-hydroxyglutamic acid, a compound found in a variety of plants which are normal constituents of the human diet; enzymic reactions in the biosynthesis of isopropanolamine, a part of Vitamin B12; new liver and kidney alsolases and dehydrogenases as well as mutant enzymes; and the metabolic significance of aminoacetone formation and urinary excretion by humans. New metabolic intermediates will be isolated and characterized, new or unusual enzymes fractionated and, hopefully, obtained in pure form, and the roles of each determined in normal and abnormal metabolism. Other studies will examine structure/function relationships of alpha-keto-gamma-hydroxyglutarate aldolase, a novel enzyme having both aldolase and beta-decarboxylase activities, and also of L-threonine dehydrogenase, an enzyme which catalyzes a unique oxidative decarboxylation of an essential amino acid for man.